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Injectable collagen scaffold promotes swine myocardial infarction recovery by long-term local retention of transplanted human umbilical cord mesenchymal stem cells

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Abstract

Stem cell therapy is an attractive approach for recovery from myocardial infarction (MI) but faces the challenges of rapid diffusion and poor survival after transplantation. Here we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic MI. Forty-five minipigs underwent left anterior descending artery (LAD) ligation and were equally divided into three groups 2 months later (collagen scaffold loading with human umbilical mesenchymal stem cell (hUMSC) group, hUMSC group, and placebo group (only phosphate-buffered saline (PBS) injection)). Immunofluorescence staining indicated that the retention of transplanted cells was promoted by the collagen scaffold. Echocardiography and cardiac magnetic resonance imaging (CMR) showed much higher left ventricular ejection fraction (LVEF) and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after treatment. There were also higher densities of vWf-, α-sma-, and cTnT-positive cells in the infarct border zone in the collagen/cell group, as revealed by immunohistochemical analysis, suggesting better angiogenesis and more cardiomyocyte survival after MI. Thus, the injectable collagen scaffold was safe and effective on a large animal myocardial model, which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI.

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Acknowledgements

This work was supported by the Key Research Program of the Chinese Academy of Sciences (ZDRW-ZS-2016-2-2), the National Key Research and Development Program of China (2016YFC1000808), the National Natural Science Foundation of China (81370239), the Key Project supported by Medical Science and Technology Development Foundation, Nanjing Department of Health (201605016), the Key Project supported by Nanjing Medical Science and Technique Development Foundation (QRX17044), and the Youth Innovation Promotion Association CAS Project (2016096).

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Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Qiang Wang, Xiaojun He, Jun Pan & Dongjin Wang

  2. Center for Clinical Stem Cell Research, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Bin Wang & Liudi Wang

  3. Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266021, China

    Chunying Shi

  4. Department of Cardiology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Jie Li

  5. Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, China

    Yannan Zhao & Jianwu Dai

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Wang, Q., He, X., Wang, B. et al. Injectable collagen scaffold promotes swine myocardial infarction recovery by long-term local retention of transplanted human umbilical cord mesenchymal stem cells. Sci. China Life Sci. 64, 269–281 (2021). https://doi.org/10.1007/s11427-019-1575-x

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